Plasma microRNA profiling: Exploring better biomarkers for lymphoma surveillance

• Published in: PloS one Vol. 12; no. 11; p. e0187722
• Main Authors: Khare, Drirh, Goldschmidt, Neta, Bardugo, Aya, Gur-Wahnon, Devorah, Ben-Dov, Iddo Z., Avni, Batia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.11.2017; Public Library of Science (PLoS)
• Subjects: Adult; Adults; Aged; Aged, 80 and over; AKT protein; B-cell lymphoma; Biological markers; Biology and life sciences; Biomarkers; Biomarkers, Tumor; Biopsy; Bone marrow; Cancer therapies; Care and treatment; Case-Control Studies; Cell division; Diagnosis; Disease; Female; Gene expression; Gene sequencing; Genetic aspects; Hematology; Hodgkin Disease - blood; Hodgkin Disease - genetics; Hodgkin Disease - pathology; Hodgkin's disease; Hodgkin's lymphoma; Humans; Hypertension; Immunotherapy; Interleukin 8; Kinases; Laboratories; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - blood; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medical diagnosis; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - blood; Middle Aged; miRNA; Nephrology; Non-Hodgkin's lymphomas; p53 Protein; Patients; Physiological aspects; Plasma; Plasma levels; PTEN protein; Research and analysis methods; Ribonucleic acid; RNA; Signaling; Stat3 protein; Survival; Transforming growth factor-b; Tumorigenesis; Tumors; Israel; Jerusalem Israel
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187722

Early detection of relapsed lymphoma improves response and survival. Current tools lack power for detection of early relapse, while being cumbersome and expensive. We searched for sensitive biomarkers that precede clinical relapse, and serve for further studies on therapy response and relapse. We recruited 20 healthy adults, 14 diffuse large B-cell lymphoma (DLBCL) patients and 11 Hodgkin lymphoma (HL) patients at diagnosis. Using small-RNA sequencing we identified in DLBCL patients increased plasma levels of miR-124 and miR-532-5p, and decreased levels of miR-425, miR-141, miR-145, miR-197, miR-345, miR-424, miR-128 and miR-122. In the HL group, we identified miR-25, miR-30a/d, miR-26b, miR-182, miR-186, miR-140* and miR-125a to be up-regulated, while miR-23a, miR-122, miR-93 and miR-144 were down-regulated. Pathway analysis of potential mRNAs targets of these miRNA revealed in the DLBCL group potential up-regulation of STAT3, IL8, p13k/AKT and TGF-B signaling, and potential down-regulation of the PTEN and p53 pathways; while in the HL group we have found the cAMP-mediated pathway and p53 pathway to be potentially down-regulated. Survival analyses revealed that plasma levels of miR-20a/b, miR-93 and miR-106a/b were associated with higher mortality. In conclusion, we identified sets of dysregulated circulating miRNA that might serve as reliable biomarkers for relapsed lymphoma.